Selenophosphate (SeP), the energy-rich selenium compound required for synthesis of specific selenocysteine-containing enzymes, can be formed by some but not all SeP synthetases from ATP and free selenide. Provision of "selenane selenium" directly to the SeP synthetase by a selenium delivery protein avoids use of highly toxic free selenide. Because Methanococcus vannielii grows anaerobically on formate as sole carbon source and must synthesize considerable amounts of several metabolically essential selenoenzymes, it was selected as a source of Se precursors and accessory proteins. A selenocysteine lyase was purified from cell extracts and the pure protein was shown to deliver Se from selenocysteine directly to the abundant M. vannielii SeP synthetase and also Escherichia coli SeP synthetase. The amino acid sequence of the lyase indicated a close relationship to NIFS sulfur delivery proteins. Another protein purified from M. vannielii exhibited sequence homology to the homocysteine synthase and cystathione lyase protein family, thus linking selenomethionine as the Se source. An unidentified Se-75 binding protein purified from M. vannielii will be tested for its ability to deliver inorganic forms of Se for selenoprotein synthesis. One of the important redox regulatory systems in plants, animals, and bacteria consists of thioredoxin and thioredoxin reductase. Recently, we discovered that the mammalian thioredoxin reductase is a selenoenzyme that contains selenocysteine. Ongoing investigation of the properties and function of the selenocysteine residue confirm its essential role in catalysis. By comparison a mutant enzyme in which selenocysteine is replaced with cysteine is a very poor catalyst. Attempts to optimize the production of the selenoenzyme in hosts other than Escherichia coli are currently in progress.